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Montelukast going to phase 1 trial.
Larrytherunner
Posted: Saturday, July 16, 2016 1:27 PM
Joined: 2/26/2016
Posts: 242


I just saw it on the web today. IntelGenx Technologies, a Canadian corporation, announced that is sponsoring the generic montelukast in clinical trials as a treatment for Alzheimer's with plans to complete phase 1 in Sept 2016 and begin recruiting for phase 2 trials soon afterward. 

Since the drug has already gone through FDA trials for asthma, and has been on the market for over 15 years with a very good safety record, I think the the trials could be completed in less time, say a couple of years. I hope they can go through without delay.

As you may know, I have already posted my self treatment with this drug. I have been taking montelukast (Singulair) 10mg twice a day for the past 6 months, and the extreme mental fatigue that had experienced before has completely gone away, and I feel normal again with no bad side effects.

This drug is being sponsored by a relatively small company in the pharma world, and I hope that it will not get side tracked by the pharma giants who have their own Alzheimer's drugs in the pipeline and don't want a cheap generic to stand in the way of their future profits. Often today if a small drug company has something that the pharma giants want, they get taken over.

I hope that the trials are completed and are successful, and patients have access to a safe, effective, and affordable treatment.

As for me, I will continue to buy montelukast as an asthma drug and use it off label.

 http://m.marketwired.com/press-release/intelgenx-to-initiate-phase-1-trial-of-montelukast-otcqx-igxt-2142090.htm


Serenoa
Posted: Monday, July 18, 2016 6:19 AM
Joined: 4/24/2012
Posts: 484


Thank you for that information Larry, and for sharring your personal experience with the drug. Anticdotal acounts like yours can be invaluable. I wish you well with it and hope you will keep us updated.

 

 I had not heard of Montelukast before, so I did a little digging on Google Scholar. It seems the drug works by inhibiting a receptor for Leukotriene, an inflammatory molecule. Inflammation is a well know factor in AD. I think Leukotriene is made mostly from omega-6 fatty acids which are known to be excessive in the American diet and lead to inflammation. But more interesting than that, is the Leukotriene receptor that the drug inhibits seems to be connected to a G Protien which when activated leads to the breakdown of the cell membrane and the creation of various molecules suspected in causing AD. These are the same factors we have been discussing in the recent post titled Associations Between Cholesterol and Alzheimer's. So, the drug may have merit. JUST TO BE CLEAR, I don't expect anyone to take this drug based on my information. These possible connections are just from me looking at Wikipedia and a few research articles.


Serenoa
Posted: Sunday, September 4, 2016 6:36 AM
Joined: 4/24/2012
Posts: 484


A little more on this potential link to inflammation. If we can understand better the causes of inflammation (which is an undisputed component of AD) then we can better choose methods of prevention and treatment. Let me post two interesting studies that may help determine why ApoE4 and high fat lead to inflammation through the involvement of Leukotrienes.



Serenoa
Posted: Sunday, September 4, 2016 6:38 AM
Joined: 4/24/2012
Posts: 484


Here's one:


5-Lipoxygenase Pathway, Dendritic Cells, and Adaptive Immunity

 "5-lipoxygenase (5-LO) pathway is the major source of potent proinflammatory leukotrienes (LTs) issued from the metabolism of arachidonic acid..."

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC548806/

 
Serenoa
Posted: Sunday, September 4, 2016 6:44 AM
Joined: 4/24/2012
Posts: 484


I was having trouble posting them together. Here's the other:


5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alpha–induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice

http://onlinelibrary.wiley.com/doi/10.1002/hep.23463/full


Lane Simonian
Posted: Monday, September 5, 2016 10:00 AM
Joined: 12/12/2011
Posts: 4986


Yes. leukotrienes activate a g protein-coupled receptor and this contributes to inflammation and oxidative stress.  

Peroxynitrite also contributes to the formation of leukotrienes via PLA2.

Phospholipase A2 (PLA2) releases lipoxins and leukotrienes from endogenous sources.

Peroxynitrite-mediated release of arachidonic acid from PC12 cells

A short term exposure of PC12 cells to a concentration of tert-butylhydroperoxide (tB-OOH) causing peroxynitrite-dependent DNA damage and cytotoxiticity promoted a release of arachidonic acid (AA) that was sensitive to phospholipase A2 (PLA2) inhibitors and insensitive to phospholipase C or diacylglycerol lipase inhibitors...These results are consistent with the possibility that endogenous as well as exogenous peroxynitrite promotes activation of PLA2.